Chapter 3: Leukocyte Circulation and Migration into Tissues There is a method to the circulation… Important points: Activated leukocytes - Naive leukocytes - Leukocyte activation and migration into infected tissueIntroduction to the major players: Selectins: ! P-selectins and E-selectins ! L-selectins Integrins: ! two noncovalently linked polypeptide chains ! mediate cell-cell adhesion or cell-ECM adhesion ! LFA-1 ! VLA-4 Chemokines and their receptors: ! CC or CXC ! leukocytes, epithelial cells, endothelial cells, fibroblasts ! GPCRs ! Chemokine functions: Abbas, Lichtman and Pillai8_Figure 3-1; p.36Leukocyte Extravasation – Innate Immune System **Please note: The above diagram is showing how neutrophils extravasate out of the blood vessels and into the surrounding infected tissues. However, a very similar mechanism is used for monocyte and T cell exit from the blood vessels into surrounding tissue. More later…stay tuned! Immunodeficiencies: leukocyte adhesion deficiencies (LAD) Please take a look at Table 3-2; we will try to keep the # of chemokines to a minimum Abbas, Lichtman and Pillai8_Figure 3-3; p.41What is inflammation? Who are the players involved? What stimulates inflammation? ! proinflammatory cytokines – Abbas, Lichtman and Pillai8_Figure 4-15; p.79Circulation through the lymph node **Please review the following structures and their locations: primary lymphatic follicle, secondary lymphatic follicle, germinal center, paracortex, and the medulla. Abbas, Lichtman and Pillai8_Figure 2-13; p.29 Abbas, Lichtman and Pillai8_Figure 2-14; p.30Lymphatic Circulation **Please note: this diagram only shows lymph nodes, not the other secondary lymphatic organs. Abbas, Lichtman and Pillai8_Figure 3-4; p.43Effector lymphocyte circulation ! LFA-1 ! CCL19 and CCL21 ! proof of concept: Abbas, Lichtman and Pillai8_Figure 3-6A, p.46 Abbas, Lichtman and Pillai8_Figure 3-6B, p.46How do leukocytes leave the lymph nodes? The players involved: ! sphingosine 1-phosphate (S1P) ! S1PR1 **S1PR1 levels vary Preferential selection Abbas, Lichtman and Pillai8_Figure 3-7, p.47How do B cells move through the body? ! CXCR5 ! CXCL13 ! CXCR4 and CCR7 ! CXCL12 and
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